FERO Grants

• Dr. Direna Alonso Curbelo, researcher at the Institute for Research in Biomedicine (IRB) in Barcelona

• Project: “Intercepting onco-inflammatory networks in pancreatic cancer”

• Grant: 80.000€

Dr. Alonso Curbelo's project will identify new factors and processes resulting from aberrant cooperation between oncogenic mutations (such as KRAS) and inflammation. This combination initiates and feeds pancreatic cancer, and the project seeks to better understand the mechanisms involved in the development of these tumors, characterize the factors that lead to immunosuppression and subsequent tumor development, and also evaluate potential targets for cancer. treatment. The proposal seeks to analyze the molecular, cellular and tissue mechanisms by which oncogenic mutations and environmental signals (pancreatitis) drive and feed Ductal Pancreatic Adenocarcinoma (PDAC), which is the fourth cause of cancer mortality in the EU, with a 5-year survival rate less than 10%.

Aid granted in collaboration with:

• Dr. Ana Ortega-Molina, researcher of the Severo Ochoa Centre for Molecular Biology -CSIC)

• Project: “Targeting unfolding protein response in high-grade B cell lymphomas”

• Grant: 80.000€

The aim of this project is to provide new strategies to treat aggressive B-cell lymphomas, which have shown poor results with standard therapies to date. Diffuse B-cell lymphoma is the most common malignant lymphoma. This is a heterogeneous group of tumours, some of which are fatal or have very poor prognosis, which are also unresponsive to current treatments. Unfolded protein response (UPR) is a cell survival pathway induced by the accumulation of misfolded or unfolded proteins. It is known that regulation of this pathway is altered in some tumours, particularly in aggressive B-cell lymphomas, but the consequences of these abnormalities are not characterised in detail. The aim of this project is to understand the signalling pathway in order to determine the response in this type of lymphoma and to identify vulnerabilities that could be used to develop new therapeutic targets.

With the contribution of Bristol Myers Squibb (BMS):

• Dr. Manel Juan i Otero, researcher at Hospital Clínic de Barcelona/IDIBAPS

• Project: ” Developing a more personalized immunotherapy in breast cancer by tracking TcR of Tumor Infiltrating Lymphocytes (TILs)”

• Grant: 80.000€

Dr. Juan’s project aims to achieve personalised immunotherapy treatments that obtain better results and prevent patient relapses. The aim is to combine the power of the TIL cells with the personalised T-cell engineering to increase the likelihood of success in patients with breast cancer. In addition to the benefit for the individual patient involved, the T-cell products specific to that patient will be used and naturally expanded TCRs will be obtained that could be used in other HLA-matched patients (with the same human leukocyte antigen) who are unable to undergo a tumour biopsy or surgery for whatever reason.

With support from MANGO.

• Dr. Aleix Prat Aparicio, researcher at Hospital Clínic de Barcelona/IDIBAPS

• Project: ” Identification of biomarkers of response to immunotherapy in hormone receptor positive/HER”

• Grant: 80.000€

His project aims to use genomics and liquid biopsy to identify which patients with hormone-sensitive breast cancer benefit from immunotherapy in combination with chemotherapy. The results will allow to implement effective therapies adapted to each subtype of breast cancer.

• Dr. Berta Casar Martínez, researcher at the Institute of Biomedicine and Biotechnology of Cantabria

• Project: ” Development of a therapeutic response marker for metastatic melanoma”

• Grant: 80.000€

Dr. Casar’s project is aimed at establishing a new biomarker predictive of the response to treatment in melanoma. This involves developing a new diagnostic kit able to predict the onset of resistance to conventional melanoma treatments. The use of this biomarker in clinical practice will allow for better stratification and personalised treatment of patients with melanoma. With the development of this new biomarker, it will be possible to identify the tumours that are likely to respond to treatment. As a result, patients will be able to benefit from more effective treatment according to their tumour and avoid unnecessary adverse effects.

With support from:

• Dr Verónica Rodilla, researcher at the Josep Carreras Research Institute

• Project: “Tumor heterogeneity comprehension for an improved diagnosis and better treatment choice for breast cancer”

• Grant: 80.000€

This project focuses on applying personalised medicine to research into two very specific types of breast cancer: that known as “triple negative”, due to being highly aggressive, and “luminal breast cancer”, which is less aggressive but one of the most common in Spain. The aim is to identify reliable biomarkers for three types of mammary epithelial cells, which will enable more precise subclassification of tumours and to determine which cells respond better to current treatments and which are more prone to cause metastasis, so that more patients with these cancer subtypes can be considered “eligible” for targeted therapies.

With support from ghd.

• Dr Nicolás Herranz, Vall d’Hebron Institute of Oncology (VHIO).

• Project: “Exploiting therapy-induced senescence in a synthetic lethal approach to treat advanced Prostate Cancer”

• Grant: 80.000€

This research aims to establish new therapeutic strategies for patients with advanced prostate cancer, based on the capacity of some current therapies to induce senescence in cancer cells (the process of cells ageing until they stop dividing, but without dying). The conversion of tumour cells into senescent cells is initially beneficial to patients as, although the cells are still alive, they are unable to proliferate. However, we know that, if these senescent cells persist over time, they may eventually encourage tumours to become resistant to therapy and regrow. The aim of this project is to find new drugs or combinations that neutralise the senescent cells and thereby prevent resistance to therapy in the context of prostate cancer.

With support from the Ramón Areces Foundation.

• Dr Verónica Torrano, University of the Basque Country.

• Project: “Targeting PGC1α-driven transcriptional landscape for personalized prostate cancer therapy”

• Grant: 80.000€

This research focuses on understanding how an aggressive prostate cancer linked to loss of transcriptional regulator PGC1α acts at the genetic and biological level. This oncogene transcriptional regulator can slow tumour growth, reducing tumour aggressiveness and increasing the natural immune response capacity. The aim of the project is to understand how PGC1α acts, to discover features of aggressiveness in patients affected by this type of tumour, based on the anti-tumour function of PGC1α, and to develop new therapies that, in combination with oncogene inhibitor treatments, boost this immune response.

With support from the Bosch Aymerich Foundation.

• Dr. Cristina Mayor Ruiz, researcher at the Institute for Research in Biomedicine (IRB) in Barcelona.

• Project: “Targeted Protein Degradation: drug discovery innovation for cancer treatment”

• Funding: €80,000

The research project has won the award thanks to its innovation in researching new treatments for cancer. Until now, the development of anti-cancer drugs has been focused on the search for inhibitors to block proteins with accessible pockets; treatments that leave out the rest of the cell's proteins. The IRB project seeks to investigate new drug-transforming paradigms through targeted protein degradation (TPD).

• Dr. Laura Belver, researcher at the Josep Carreras Institute.

• Project: "Molecular pathways and targeted therapies in Juvenile Myelomonocytic Leukemia"

• Funding: €80,000

This project works to develop targeted therapies to reverse the activity of the SHP2 protein. This protein is encoded by the gene PTPN11, the gene where the most common genetic alteration occurs in juvenile myelomonocytic leukemia, a type of hematological cancer that mainly affects children under the age of two. Approximately 40% of patients present mutations in the PTPN11 gene that are also associated with the more aggressive forms of the disease, to the point that only one in four children with this genetic alteration survive. At present, there are no specific therapies to treat these patients. Thus, the main objective of our research is to develop new therapeutic strategies specifically designed for children affected by this type of leukemia.

• Dr. Esteban Veiga Chacón, researcher at the National Center of Biotechnology, part of the Spanish National Research Council (CNB-CSIC)

• Project: "Next generation of cancer immunotherapies based on bacteria-trained lymphocytes"

• Funding: €80,000

This project focuses on consolidating the data on the effectiveness of bacT cells (lymphocytes trained with bacteria) as a novel immunotherapy to combat tumors, with a specific focus on breast cancer. If CAR-T cells can be reactivated, it would be a big step towards new therapies for solid tumors, a field where this technique has not been successful so far. The project also aims to generate new algorithms for the identification of tumor neo-antigens (identifiers that we would attach to bacteria to enable our immune system to recognize cancer cells), one of the greatest challenges in tumor immunotherapy.

• Dr. Antoni Celià-Terrassa, researcher at the Hospital del Mar Institute for Medical Research (IMIM)

• Project: "Double-edge therapy targeting metastasis-initiating cells and immune cells"

• Funding: €80,000

The research is specialized in the study of metastatic initiating cells (MICs). The project's aim is to use advanced imaging technology, RNA sequencing and computational biology to analyze how a patient's metastasis evolves, by blocking a co-inhibiting receptor of immune cells that can influence their pro-metastatic function and immune resistance.

• Dr. Antonia Tomas-Loba, researcher at the University of Murcia

• Project: "Circadian Rythm, Liver Cancer and beyond"

• Funding: €80,000

The research seeks to better understand the origin of liver cancer by investigating the molecular relationship between the disruption of circadian rhythms and the occurrence of liver cancer. Liver cancer is the 3rd leading cause of cancer death worldwide and its incidence is expected to increase by 62% by 2040. The causes are closely related to our pace of life and the constant breaking of natural cycles such as circadian rhythms (declared as a carcinogenic agent by the WHO and the IARC).

• Dr. Raquel Pérez, researcher at Vall d'Hebron Institute of Oncology (VHIO)

• Project: “Unravelling the tumor immunophenotype with deep-learning radiogenomics”

• Funding: €80,000

This research aims to develop an algorithm that, using artificial intelligence, correlates the CT image of the tumor's characteristics, with the patient's immune profile and response to immunotherapy. The aim of this being that by simply applying this algorithm in the future it will be possible to more effectively personalize treatment for each patient, selecting the patients who will benefit from immunotherapy and identifying earlier and more effectively whether the patients are responding or not.

• Dr. Cristina Saura and Dr. Miriam Sansó, researchers at Vall d'Hebron Institute of Oncology (VHIO)

• Project: "ctDNA in breast milk for early detection of Pregnancy Associated Breast Cancer"

• Funding: €80,000

This research considers an innovative use of liquid biopsy in breast milk. The aim is to validate the use of breast milk for the early detection of pregnancy associated breast cancer in order to help improve the current prognosis of this disease. Breast cancer during pregnancy and postpartum is difficult to diagnose due to the changes that the breast undergoes during gestation and the limits placed on imaging tests to protect the fetus during this period. In order to diagnose these tumors at curable stages, this project aims to detect ctDNA derived from the tumor and identified in breast milk.

• Dr. Priscila Monteiro Kosaka, Researcher at CSIC.

• Project: New devices at the frontier between nano-mechanics and nano-optics for the detection of next-generation biomarkers for lung cancer through blood analysis.

• Funding: €80,000

This research aims to develop a new technology for the identification of biomarkers enabling early detection and treatment of lung cancer through a blood analysis. The study focuses on developing a hybrid technology combining two powerful nanotechnologies, nano-mechanics and nano-optics, for the detection of fusion proteins, responsible for cancer development and growth. Currently, detection of this kind of proteins, which are found at ultra-low concentrations, is only possible by means of a biopsy, an invasive procedure that cannot be used in advanced disease stages. The project aims to develop a highly sensitive technology capable of identifying fusion proteins through a simple blood analysis, in order to establish biomarkers enabling more effective diagnosis and treatment of lung cancer.

• Dr. Roger Gomis, Professor of ICREA at the Institute for Research in Biomedicine (IRB) of Barcelona.

• Project: Identification of pro-metastatic properties of luminal breast cancer of fibroblasts derived from MSC cells.

• Funding: 80,000€

The research focuses on the study of luminal breast cancer, one of the most common subtypes of breast cancer, in which it has been observed that metastases occur mainly in the bone. This type of cancer may produce metastases after long disease-free spells and cause death in a very short period of time. A possible interaction between tumour cells which produce the metastasis of this type of cancer and fibroblasts derived from MSC cells located in the bone has been observed in recent years. These interactions have an influence on the tumour and may be behind metastatic relapse and condition the disease’s response to systemic therapy. The project aims to study these interactions in order to increase knowledge, establish therapeutic targets and limit the capacity of these cells to produce metastasis.

• Dr. Asís Palazón, Researcher at CIC bioGUNE in Bilbao.

• Project: Placing the focus on immune system epigenome for the next generation of immuno-oncology.

• Funding: €80,000

Although immunotherapy has been the most promising cancer treatment since the development of the first chemotherapies, currently available techniques are only effective in a certain group of patients, and several combined clinical approaches have recently failed. Therefore, it is essential to find new targets that can contribute to the improvement of the current effectiveness in immunotherapy treatments.

This study focuses on identifying new aberrant epigenetic modifications that prevent the correct formation of long life memory cytotoxic T-cells –immune cells of the tumour microenvironment (TME) capable of destroying cancer cells– and thus precipitating their exhaustion. Based on the finding of such alterations in normal cytotoxic T-cells, which could be related to a deficient oxygen supply required to carry out their mission, the researchers aim to also discover mechanisms capable of rejuvenating exhausted T-cells in TME, opening up new therapeutic targets which contribute to improve the effectiveness of immunotherapy.

• Dr. Joaquin Mateo, Researcher at Vall d’Hebron Institute of Oncology (VHIO).

• Project: New approaches to liquid biopsy in prostate cancer to inform precision medicine.

• Funding: €80,000

The project focuses on discovering whether a liquid biopsy analysis integrating circulating tumour cells (CTC), circulating tumour DNA (ctDNA) and exosome tumour DNA (exoDNA) can be effective as a non-invasive prognostic and predictive method in prostate cancer. This research seeks to improve clinical results in patients through a more precise and personalised care based on the study of the evolution of prostate cancer through non-invasive analyses –a sample of plasma collected before and during treatment would suffice –, thus overcoming the limitations involved in repeated tumour biopsies in order to determine the evolution of the tumour in each patient.

• Dr. Violeta Serra and Dr. Judith Balmaña from Vall d’Hebron Institute of Oncology (VHIO).

• Project: Development of a liquid biopsy test to determine the functional state of homologous recombination in carriers of mutation BRCA1/2 in breast cancer to help in therapy selection.

• Funding: €80,000

The project aims to discover whether liquid biopsy can be useful to optimise a test to identify the most sensitive tumours and monitor the response to treatment in breast cancer patients with a mutation in genes BRCA1/2. Tumours with this mutation are not able to correctly repair certain DNA errors and are, therefore, extremely sensitive to a type of targeted therapy using poly(ADP-ribose)-polymerase (PARPi) inhibitors. However, the tumour may lose this sensitivity when it evolves. In fact, it has been noticed that 40% of metastatic tumours present intrinsic resistance and the majority of sensitive cases eventually progress. The work seeks to develop a sensitivity test which can be used in liquid biopsies. This achievement would enable a longitudinal monitoring of response to treatment in a less invasive manner than with tumour biopsies. This would entail prescription of more beneficial treatment for each patient and would also reduce the indication of ineffective ones.

• Dr. Bruno Sainz, Biomedical Research Institute at Autonomous University of Madrid (UAM)

• Project: Combating pancreatic cancer through the identification of essential tumourigenicity genes induced by cancer stem cells.

• Funding: €80,000

Cancer stem cells (CSC) are extremely important for tumourigenicity, metastasis and therapeutic resistance. This project pursues three main objectives: identifying the genes responsible for self-renewal and tumorigenesis of pancreatic CSC; validating candidate genes through in vivo and in vitro models; proving the clinical relevance of altering key candidate genes (pharmacologically or genetically) in combination with other targets in preclinical murine models with pancreatic ductal adenocarcinoma (PDAC).

The study is being conducted through a sophisticated genetic approach, focused and targeted to identify the set of key genes dictating CSC state, in order to facilitate the development of personalised therapies against CSC. The results are expected to have a very significant socioeconomic impact, considering that PDAC is the most deadly of all solid tumours and there is currently no effective treatment.

• Dr. Alejo Efeyan. Researcher at National Oncological Research Centre (CNIO)

• Project: Exploring dependencies in the signalling and metabolism of lymphoma B cells.

• Funding: €80,000

It is known that tumours need high levels of nutrients, but not which tumours require which nutrients. The project aims to fill this knowledge gap in order to develop new treatments based on two complementary therapeutic strategies: selectively supressing the nutrients required by tumours in order to weaken them and, in parallel, stopping the tumours from detecting the absence of those nutrients to prevent them from switching on and off the genes enabling them to adapt and survive under conditions of nutrient fluctuation.

Gene mutations signalling high levels of certain nutrients to tumour cells have been identified in mouse lymphomas. These mutations lead tumour cells to believe that high levels of amino acids are available, causing them to grow and multiply. It has been noted that these mutations accelerate the appearance of lymphoma. By using a drug to block the cellular circuit connecting the detection of nutrients with cellular multiplication, it has been observed that the presence of these mutations makes tumour cells vulnerable. The next step is to confirm whether that weakness also exists in human lymphomas.

• Dr. Berta L. Sánchez-Laorden. Developmental Neurobiology Unit at Neuroscience Institute of Alicante, joint centre CSIC-UMH

• Project: Identifying new therapeutic approximations for cerebral metastasis of melanoma.

• Funding: €80,000

Many melanoma patients develop brain metastasis, which substantially reduces their life expectancy. This project aims to uncover vulnerable points of cerebral metastasis of melanoma that may be targeted and which enable new and more effective treatments.

The study has established preclinical models of cerebral metastasis of melanoma in order to understand its biology and evolution of the immune brain component during the progression of metastasis and in response to treatment. The project is characterising the interaction between different components of the immune system with melanoma cells in the brain and test whether blocking that communication may reduce the progression of cerebral metastasis and improve therapeutic response.

• LDr. Alena Gros. Head Researcher in the Tumour Immunotherapy and Immunology Group at VHIO (Vall d’Hebron Institute of Oncology, Barcelona)

• Project: Non-invasive and personalised T-cell therapy aimed at recurrent target mutations.

• Funding: €80,000

Cancer immunotherapy makes use of the immune system which protects us from infections and other pathologies to attack cancer. T-cells are capable of recognising and eliminating tumours with exquisite specificity by recognising mutated tumour proteins, as a result of the accumulation of genetic alterations occurring during tumour development. These lymphocytes, known as neoantigen specific, play an important role in the effectiveness of immunotherapy. Given their capacity to attack and eliminate tumours in a highly specific manner, the project’s aim is to develop personalised cellular therapies, based on the administration of large amounts of T-cells specific against neoantigens. To this end, the project will study the presence of T-cells which recognise mutated peptides derived from proteins that are commonly found mutated in cancer patients, such as KRAS. Once identified, the T-cell receptors responsible for conferring antitumor specificity to lymphocytes will be cloned and introduced into a viral vector in order to induce receptor expression in peripheral blood lymphocytes. This should generate a significant amount of T-cells capable of recognising specific tumour mutations. Isolating various specific receptors against frequently mutated proteins in cancer will enable the development of cellular therapies to treat patients with metastatic disease with no therapeutic alternatives.

• Dr. Alberto Jiménez Schumacher. Head of the Molecular Oncology Group at Healthcare Research Institute of Aragón (IIS Aragón), Zaragoza.

• Project: Virtual Biopsy: development of non-invasive immunotargeted imaging agents for the diagnosis of glioblastoma.

• Funding: €70,000

Biomedical imaging consists of photographs that help doctors make decisions (X-rays, ultrasound scans). The technique of positron emission tomography (PET) can obtain 3D images by detecting physical particles known as positrons. There are currently very few agents that can be detected through PET, mainly a carbohydrate (FDG) which emits positrons. Since tumour cells uptake higher quantities of sugar, it is possible to detect small tumours and metastases. However, for cerebral tumours this PET is so limited as to not be effective, because our brain consumes large amounts of sugar. Survival of glioblastoma, the most lethal cerebral tumour, is scarcely 15 months, and taking an intracranial biopsy to confirm the diagnosis, in addition to entailing significant risk, is not sufficient because these tumours are very heterogeneous mosaics.

The project aims to enable better PET images in order to detect and obtain more information about these cerebral tumours. The idea is to have a “virtual biopsy” providing the same information as several biopsies, but through non-invasive imaging tests. This technique would make it possible to have information about the anatomy and geography of the tumour, its grade and response to possible treatment.

• Dr. Clara Bueno. Researcher at Josep Carreras Research Institute against Leukaemia.

• Project: Adaptive immunotherapy with CAR-NG2 T-cells for acute leukaemia with MLL reordering.

• Funding: €70,000

Acute lymphoblastic leukaemia with a lymphoid (ALL) and myeloid (AML) origin are very difficult to treat in cases of relapse or resistance to treatment. However, over the past three years, the therapeutic application of CART cells has brought about a revolution. The transfer of CART cells targeting a surface molecule of specific tumour cells is a new and interesting approach for immunotherapy against cancer.

This project has conducted necessary preclinical trials to demonstrate the effectiveness of CART for the treatment of LMA with MLL reordering. In terms of infant LLA, the team has managed to block antigen NG2 and registered a European patent on its therapeutic use. At present, the work is focusing on developing a strategy based on the use of CART to prevent relapse in LLA patients.

• Dr. María Abad. Researcher at the Cancer and Cellular Plasticity Group of VHIO (Vall d'Hebron Institute of Oncology , Barcelona).

• Project: Identification of new micropeptides involved in pancreatic cancer: new players for new therapies.

• Funding: €70,000

There is significant interest in understanding how to inactivate cellular plasticity (the capacity of tumour cells to transform and change their properties). This project focuses on pancreatic cancer, one of the most deadly tumours, and seeks to identify new key micropeptides in tumour plasticity and progression. Micropeptides are small proteins which had been overlooked until recently, but are currently believed to play a significant role in cancer. The work aims to increase the knowledge of pancreatic cancer and understand why current therapies are failing. In addition, the discovery of new micropeptides could open a door for the development of new antitumor therapies. The ultimate goal is to provide relevant information in oncological research that may eventually result in better treatments for cancer patients.

Currently, the team has identified five new micropeptides and the results obtained show that all of them play a role in suppressing tumours, inducing death of tumour cells, arresting their division and preventing them from invading other tissues.

• Dr. Héctor Peinado. Group Leader at the Spanish National Cancer Research Centre (CNIO).

• Project: Liquid biopsy in exosomes: predicting the response to (immune and radio) therapies.

• Funding: €70,000

Up to 50% of melanoma patients suffer relapse and there are currently no prognostic markers to identify those at risk. The present study aims to develop methods to identify residual disease after surgery in melanoma patients who could benefit from early diagnosis and specific therapies.

The project is based on the use of liquid biopsy (similar to blood analysis) for the prognosis of melanoma patients using vesicles and DNA circulating in plasma and lymphatic fluid of melanoma patients in order to obtain molecular signatures associated to disease progression and thus improve their treatment. This approach serves as a real time liquid biopsy at the time when patients are discharged after surgery to resect lymph nodules (a procedure known as lymphadenectomy).

• Dr. Beatriz Morancho. Cancer researcher, cellular and molecular biologist working at the laboratory of Dr. Joaquín Arribas at VHIO (Vall d’Hebron Institute of Oncology, Barcelona)

• Project: Immunotherapy to treat breast and colorectal cancer.

• Funding: €70,000

• Anonymous sponsor

The immune system is capable of recognising and eliminating tumour cells, although some of them are able to evade detection and survive. One of the most promising strategies in the development of new anti-tumour therapies is to enhance this recognition by establishing physical contacts between immune and cancer cells, in order to facilitate the death of the latter through the use of bispecific (TCBs) antibodies.

The project seeks to identify biomarkers for sensitivity and resistance to two bispecific antibodies, one recognising p95HER2 and another CEA, focusing on breast and colon cancer, respectively. It was proven that p95HER2-TCB had a potent anti-tumour effect and it was defined which patients would benefit from this treatment, currently in preclinical phase. In addition, since p95HER2 is not expressed in normal tissues, it would be possible to avoid one of the main drawbacks of these therapies, namely the recognition of non-tumour tissue targets. At the moment, studies are focusing on the mechanisms of resistance against TCBs that may appear.

• Dr. Manuel Valiente. Group Leader at the Spanish National Cancer Research Centre (CNIO).

• Project: Research of cerebral metastasis caused by lung cancer.

• Funding: €70,000

• Anonymous sponsor

Small cell lung cancer is associated with a very high rate of brain metastasis. Available treatments for such cases of brain metastasis caused by lung cancer are limited and have modest benefits for patients. This research project studied the biology of brain colonisation with the goal of developing new treatments for cerebral metastasis.

The project developed a new model of small cell lung cancer in order to study the process of metastasis generation by induction of the primary tumour. The model obtained was a pioneering one and is currently an essential laboratory tool that is being used in several other projects including: characterisation of new metastasis inhibitors; determination of molecular mechanisms required for adaptation and growth in the brain; and design and characterisation of new biomarkers compatible with non-invasive biopsies to evaluate both the incidence of cerebral metastasis and its response to therapy.

• Dr. César Serrano. Head of Translational Research in Sarcomas. VHIO (Vall d’Hebron Institute of Oncology, Barcelona).

• Project: New strategies against tumour heterogeneity in gastrointestinal stromal tumours: early detection of resistant subpopulations for rotation of targeted therapies.

• Funding: €70,000

• Anonymous sponsor

Tumours do not have the same type of alterations distributed homogeneously. This entails, on the one hand, that a single tumour sample is not necessarily representative of what is taking place within the patient and, on the other, that a single drug is often not completely effective against the large variety of mechanisms which contribute to the growth of tumours. Conversely, all tumours release their genetic material into the bloodstream, also known as circulating tumour DNA. The goal of this project is to develop liquid biopsy as a method to guide specific cancer treatments.

Using this technology, the team analysed alterations in circulating tumour DNA from blood samples of patients with gastrointestinal stromal tumours (GIST) in order to identify, in real time, which part of the tumour was causing problems to the patient and administer targeted therapies at the right time. The study of circulating tumour DNA (ctDNA) in blood samples represents another step towards personalised medicine in cancer.

• Dr. Arkaitz Carracedo. Group Leader of the Molecular Oncology Program at CIC bioGUNE in the Basque Country.

• Project: Study of new targets in aggressive breast cancer.

• Funding: €70,000

• Anonymous sponsor

Certain types of breast cancer still have a poor prognosis. This study investigated the development of the most aggressive subtype of breast cancer in order to obtain crucial information in the search for solutions. As a result, the team was able to identify a molecular marker for this type of tumour which provides information on aggressiveness and capacity to extend. This information has been essential to demonstrate that, by inhibiting this marker, aggressive breast cancer cells lose their capacity to metastasise.

These results are another step towards an international strategy of individualising treatments based on the molecular characteristics of cancer (the barcode of each tumour). The development of individualised therapies required two main tools: markers to identify tumours (the barcode reader) and drugs that work on each type of barcode.

• Dr. Sandra Peiró. Researcher at IMIM, Hospital del Mar Medical Research Institute.

• Project: Study of three-dimensional characteristics of tumour cell DNA.

• Funding: €70,000

• Anonymous sponsor

DNA molecules have three-dimensional structures and this level of organisation is closely linked to the genome’s function and, therefore, cellular function. The team believe that, in order to understand how the genome works it is necessary to integrate all the available information about it: DNA sequence, epigenetic patterns, expression patterns of noncoding RNAs and 3D genome structure, since it is this 3D structure that will determine which genes will or will not be activated during a given process.

This project contributed to the first characterisation of the 3D structure of the genome during the acquisition of metastatic properties. The work conducted demonstrated how Lamina B1 protein is necessary for the reorganisation of the genome required to transform a non-invasive cell into one capable of migrating and invading other tissues.

• Dr. Yasir Ibrahim. Postdoctoral Fellow in the Experimental Therapy Group. VHIO (Vall d’Hebron Institute of Oncology, Barcelona).

• Project: Study of predictive biomarkers and mechanisms of resistance to targeted therapies in breast cancer.

• Funding: €70,000

• Anonymous sponsor.

Despite therapeutic advances for breast cancer in recent years, there are still cases resistant to targeted therapy. This project seeks to delve into the genetic and molecular aspects that determine sensitivity and resistance to the most innovative drugs for breast cancer: PI3K and CDK4/6 inhibitor in combination with drugs approved for the treatment of hormone-dependent disease. The aim is to identify the group of patients who may benefit the most from these therapies.

The project comprises three main lines: expansion of the xenograft model; study of the anti-tumour activity of PI3K and CDK4/6 inhibitors in models derived from PDX breast cancer of the HER2 and luminal (ER-positive) subtype, through ex-vivo tests; validation of genotype/pharmacodynamic marker association with phenotype through genetic engineering and molecular biology techniques.

• Dr. Héctor G. Palmer. Head of the Cancer and Stem Cell Group. VHIO (Vall d’Hebron Institute of Oncology, Barcelona).

• Project: Study of molecular mechanisms responsible for progression of colon cancer.

• Funding: €70,000

• Anonymous sponsor

It is common for seemingly cured and disease-free patients to suffer a relapse after several years and develop far more aggressive and lethal tumours. Behind these relapses are tumour cells resistant to treatment which lie dormant. The current project aimed to isolate such cells and study their distinctive characteristics to find solutions.

The project enabled identification of a therapeutic target whose inhibition caused elimination of those chemoresistant cells. In addition, the team defined a biomarker which revealed the presence of these resistant cells in tumours before treatment. This facilitates their detection in cancer patients to conduct, for example, more frequent clinical monitoring and more prolonged adjuvant treatment.

• Dr. Laura Soucek. Head of Modelling of Anti-tumour Therapies in Mice, VHIO (Vall d'Hebrón Institute of Oncology, Barcelona)

• Project: inhibition of oncoprotein Myc present in most tumours.

• Funding: €70,000

• Sponsored by Josep Botet Foundation

Myc is a protein coordinating all programs which enables a cell to grow and divide and, is involved in nearly all types of cancer. Despite the obvious role of Myc in cancer, there is still no drug that inhibits it and this is precisely the objective of the present project.

The FERO Grant was used to finance key experiments for the development of what could become the first Myc inhibitor, Omomyc. The studies conducted demonstrated that Omomyc has a notable therapeutic index in all cancer tested types (skin, lung, pancreatic and, more recently, brain cancer). In addition, it entails no relevant or severe secondary effects in normal tissue.

• Dr. Amancio Carnero. Scientific researcher at IBIS, Seville Biomedicine Institute.

• Project: Study of personalised sarcoma treatment.

• Funding: €70,000

• Sponsored by Josep Botet Foundation

Sarcomas are malignant tumours with a high percentage of morbidity and mortality in children and adults. This research project was driven by the need to develop new treatments, with the ultimate goal of identifying predictive biomarkers for the effect of various drugs used to treat sarcomas with very scarce therapeutic options.

The project involved two main lines of action. The first sought to generate a platform of sarcoma xenograft models through the implantation of human sarcoma samples. The second worked on detecting sarcoma biomarkers in order to identify those therapies with the best effectiveness. As a result, a small window was opened to personalised medicine for sarcomas, identifying patients who may benefit from other treatments.

• Dr. Jaume Mora. Head of Paediatric Oncology at Sant Joan de Déu Barcelona Children’s Hospital.

• Project: Research against Ewing sarcoma.

• Funding: €70,000

• Sponsored by Josep Botet Foundation.

The family of Ewing sarcoma (ES) tumours is a set of primary bone and soft tissue neoplasms primarily affecting adolescents and young adults. This is a rare disease (affecting 50 individuals each year) which requires treatment at highly specialised centres. Thanks to the grant, it was possible to conduct a trial throughout Spain amongst children, adolescents and young adults, in order to generate the first treatment protocol for ES at a state level.

The clinical trial conducted was a prospective, multicentre, non-randomised study of patients with ES aged 40 or younger. All the individuals underwent a uniform treatment, which demonstrated that the results depended mainly on the biology behind each case and were notably influenced by the age at which the disease appeared, probably linked to the cell of origin and the environment in which the malignancy developed.

In conclusion, the first FERO grant was a boon for the study of this disease in Spain.